Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases

Pongali B. Raghavendra, Yashin Sreenivasan, Govindarajan T. Ramesh, Sunil K. Manna

    Research output: Contribution to journalArticle

    41 Citations (Scopus)

    Abstract

    Decrease in caspase activity is a common phenomenon in drug resistance. For effective therapeutic intervention, detection of such agents, which affects other pathway independent of caspases to promote cell death, might be important. Oleandrin, a polyphenolic glycoside induced cell death through activation of caspases in a variety of human tumour cells. In this report we provide evidence that besides caspases activation, oleandrin interacts with plasma membrane, changes fluidity of the membrane, disrupts Na+/K+-ATPase pump, enhances intracellular free Ca2+ and thereby activates calcineurin. Calcineurin, in turns, activates nuclear transcription factor NF-AT and its dependent genes such as FasL, which induces cell death as a late response of oleandrin. Cell death at early stages is mediated by caspases where inhibitors partially protected oleandrin-mediated cell death in vector-transfected cells, but almost completely in Bcl-xL-overexpressed cells. Overall, our data suggest that oleandrin might be important therapeutic molecule in case of tumors where cell death pathway occurs due to deregulation of caspase-mediated pathway.

    Original languageEnglish
    Pages (from-to)307-318
    Number of pages12
    JournalApoptosis
    Volume12
    Issue number2
    DOIs
    Publication statusPublished - 02-2007

    Fingerprint

    Cardiac Glycosides
    Calcineurin
    Cell death
    Caspases
    Cell Death
    Chemical activation
    Apoptosis
    Tumors
    NFATC Transcription Factors
    Membrane Fluidity
    Caspase Inhibitors
    Deregulation
    Fluidity
    Cell membranes
    Glycosides
    Drug Resistance
    Adenosine Triphosphatases
    Neoplasms
    Genes
    Cells

    All Science Journal Classification (ASJC) codes

    • Pharmacology
    • Pharmaceutical Science
    • Clinical Biochemistry
    • Cell Biology
    • Biochemistry, medical
    • Cancer Research

    Cite this

    Raghavendra, Pongali B. ; Sreenivasan, Yashin ; Ramesh, Govindarajan T. ; Manna, Sunil K. / Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases. In: Apoptosis. 2007 ; Vol. 12, No. 2. pp. 307-318.
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    Cardiac glycoside induces cell death via FasL by activating calcineurin and NF-AT, but apoptosis initially proceeds through activation of caspases. / Raghavendra, Pongali B.; Sreenivasan, Yashin; Ramesh, Govindarajan T.; Manna, Sunil K.

    In: Apoptosis, Vol. 12, No. 2, 02.2007, p. 307-318.

    Research output: Contribution to journalArticle

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